X-ray Crystallography experiments remain the most successful method to obtain structural information from biological targets, comprising 85737 structures out of 97180 (88%) deposited as of Jan. 21, 2014 in the protein database entries. Advances in molecular biology and biochemical techniques have allowed expression and purification of a significant number of new protein targets including human and pharmacological relevant proteins. Similarly, innovations in synchrotron science including development of micro-focused X-ray beams and advances in detector technologies as well as development of user-friendly crystallography software packages have expedited crystal-to-structure time frames. However, notwithstanding the abundance of targets or the increasingly faster crystal-to-structure pipeline, crystallization of protein targets remains the most significant bottleneck in structure determination by X-ray crystallography and continues to have significant negative impact in the field.